Technical Field
The present disclosure relates to two linear gold(I) dithiocarbamate complexes containing a R2N—CS2 thioureide bond, a method of making the linear gold(I) dithiocarbamate complexes, and a method of the cytotoxic treatment of cancer cells.
Description of the Related Art
The “background” description provided herein is for the purpose of generally presenting the context of the disclosure. Work of the presently named inventors, to the extent it is described in this background section, as well as aspects of the description which may not otherwise qualify as prior art at the time of filing, are neither expressly or impliedly admitted as prior art against the present invention.
Transition metal complexes of common ligands with group 15 (Nitrogen, Phosphorus and Arsenic) and group 16 (Oxygen, Sulfur, Selenium) donor atoms have been extensively investigated in various fields of bioinorganic chemistry, electrochemistry and organometallic chemistry. The study of gold complexes bearing different functional ligands exhibiting interesting physical, chemical, biological and pharmacological properties, has gained much attention (K. Nomiya, R. S. Yamamoto, R. Noghuchi, H. Yokoyama, N. C. Kasuga, K. Ohyama, C. Kato, J. Inorg. Biochem. 95 (2003) 208-220; T. McCormick, W. L. Jia, S. Wang, Inorg. Chem. 45 (2006) 147-155; S. S. Al-Jaroudi, M. I. M. Wazeer, A. A. Isab, S. Altuwaijri, Polyhedron. (2013) 434-442; R. B. Bostancioglu, K. Isik, H. Genc, K. Benkli, A. T. Koparal, Medicinal Chemistry. 27 (2012) 458-466—each incorporated herein by reference in its entirety).
There was substantial interest in the coordination chemistry of Au(I) complexes showing biological activity with potential medicinal applications. For instance, currently used drugs like Auranofin, Solganol and Myocrisin are Au(I)—S complexes (S. H. van Rijt, P. J. Sadler, Drug Discovery Today, 14 (2009) 1089-1097; R. Noghuchi, A. Hara, A. Sugie, K. Nomiya, Inorg. Chem. Commun. 9 (2006) 355-359; K. Nomiya, R. Noghuchi, K. Ohsawa, K. Tsuda, M. Oda, J. Inorg. Biochem. 78 (2000) 363-370; B. P. Howe, Metal Based Drugs. 4 (1997) 273-277; V. J. Ctalano, A. O. Etogo, J. Organomet. Chem. 690 (2005) 6041-6050—each incorporated herein by reference in its entirety). Consequently, gold(I) complexes have long been studied as anti-arthritic and anti-microbial agents (O. Crespo, V. V. Brusko, M. C. Giameno, M. L. Tornil, A. Laguna, N. G. Zabirov, Eur. J. Inorg. Chem. 2 (2004) 423-430; K. Nomiya, R. Noghuchi, M. Oda, Inorg. Chim. Acta. 298 (2000) 24-32; H. Q. Liu, T.-C. Cheung, S.-M. Peng, C.-M. Che, J. Chem. Soc., Chem. Commun. (1995) 1787-1788; C. J. O'Connor, E. Sinn, Inorg. Chem. 17 (1978) 2067-2071; M. A. Cinellu, G. Minghetti, M. V. Pinna, S. Stoccoro, A. Zucca, M. Manassero, M. Sansoni, J. Chem. Soc., Dalton Trans., (1998) 1735-1742—each incorporated herein by reference in its entirety). It has been found that gold(I)-phosphine complexes with P—Au—P, P—Au—N, P—Au—S, and S—Au—S bonding show marked biological activities against bacteria and yeast (K. Nomiya, S. Takahashi, R. Noghuchi, J. Chem. Soc., Dalton Trans. (2000) 2091-2097; R. C. Elder, K. Ludwig, J. N. Cooper, M. K. Eidsness, J. Am. Chem. Soc. 107 (1985) 5024-5025—each incorporated herein by reference in its entirety). Gold(I) phosphine complexes are known to exhibit promising anticancer properties (R. W.-Y. Sun, C.-M. Che, Coord. Chem. Rev., 253 (2009) 1682-1691; P. Papathanasiou, G. Salem, P. Waring, A. C. Willis. J. Chem. Soc., J. Chem. Soc. Dalton Trans., (1997) 3435-3443; H. Lv, B. Yang, J. Jing, Y. Yu, J. Zhang, J.-L. Zhang, Dalton Trans., 41 (2012) 3116-3118—each incorporated herein by reference in its entirety). In this connection, Lorber et al in 1979, firstly reported that Auranofin could inhibit the in vitro proliferation of HeLa cells (T. M. Simon, D. H. Kunishima, G. J. Vibert, A. Lorber, Cancer, 44 (1979) 1965-1975—incorporated herein by reference in its entirety). Berners-Price and coworkers reported Bis(diphosphino)gold(I) compounds and demonstrated promising in vivo anti-cancer activities (S. J. Berners-Price, C. K. Mirabelli, R. K. Johnson, M. R. Mattern, F. L. Mccabe, L. F. Faucette, C. M. Sung, S. M. Mong, P. J. Sadler, S. T. Crooke, Cancer Res. 46 (1986) 5486—incorporated herein by reference in its entirety). Again Berners-Price et al pointed out [Au(dppe)2]+ and its derivatives as their persuasive in vitro and in vivo anti-cancer activities via the mitochondrial-mediated apoptotic pathway (M. J. McKeage, L. Maharaj, S. J. Berners-Price, Coord. Chem. Rev. 232 (2002) 127-135—incorporated herein by reference in its entirety). Barnard et al recently recognized a series of gold(I) compounds with carbene ligands (P. J. Barnard, S. J. Berners-Price, Coord. Chem. Rev. 251 (2007) 1889-1902—incorporated herein by reference in its entirety).
In the first decade of the 21st century, a new class of gold complexes with dithiocarbamate ligands has emerged as anticancer agents. In this regard, Fregona and coworkers firstly prepared and characterized gold(III) dithiocarbamate compounds containing N,N-dimethyldithiocarbamate and ethylsarcosinedithiocarbamate showing a very promising chemical and biological profile (L. Ronconi, L. Giovagnini, C. Marzano, F. Bettio, R. Graziani, G. Pilloni, D. Fregona, Inorg. Chem. 44 (2005) 1867-1881—incorporated herein by reference in its entirety) Treatment with dibromo(N,N-dimethyldilhiocarbamato)gold(III) resulted in significant inhibition of in-vivo MDA-MB-231 breast tumor growth (V. Milacic, D. Chen, L. Ronconi, K. R. Landis-Piwowar, D. Fregona, Q. P. Dou, Cancer Res. 66 (2006) 10478-10486—incorporated herein by reference in its entirety). Zhang et al reported that gold(I)-dithiocarbamato species, namely [Au(ESDT)](2) could inhibit the chymotrypsin-like activity of purified 20S proteasome and 26S proteasome in human breast cancer MDA-MB-231 cells, resulting in accumulation of ubiquitinated proteins and proteasome target proteins, and induction of cell death (X. Zhang, M. Frezza, V. Milacic, L. Ronconi, Y. Fan, C. Bi, D. Fregona, Q. P. Dou, J. Cell Biochem. 109(1) (2010) 162-72—incorporated herein by reference in its entirety).
In recent years, research has increasingly focused on the potential of gold complexes as anticancer drug candidates (S. Ahmad, A. A. Isab, S. Ali, A. R. Al-Arfaj, Polyhedron. 25 (2006) 1633-1645; D. V. Partyka, T. J. Robilotto, M. Zeller, A. D. Hunter and T. G. Gray, Proc. Natl. Acad. Sci. U.S.A 105 (2008) 14293-14297; Y. Wang, Q.-Y. He, C.-M. Che, J.-F. Chiu, Proteomics. 6 (2006) 131-142; Y. Shi, W. Chu, Y. Wang, S. Wang, J. Du, J. Zhang, S. Li, G. Zhou, X. Qin, C. Zhang, Inorg. Chem. Commun. 30 (2013) 178-181; M. Monim-ul-Mehboob, M. Altaf, M. Fettouhi, A. A. Isab, M. I. M. Wazeer, M. N. Shaikh, S. Altuwaijri, Polyhedron. 61 (2013) 225-234—each incorporated herein by reference in its entirety). Gold(I) thiolates employed clinically in the treatment of rheumatoid arthritis display some potency against various tumors but a greater potential is found in their analogues. In particular, analogues featuring a linear P—Au—S arrangement in which the thiolate ligand is derived from a biologically active thiol display high potency (E. R. Tiekink, Crit. Rev. Oncol. Hematol. 42 (2002) 225-48—incorporated herein by reference in its entirety).
The synthesis of gold(I) complexes of phosphine with dialkyl dithiocarbamate mixed ligands, their structure analysis by IR spectroscopy and NMR measurements, and their structure determination by single crystal X-ray crystallography is disclosed herein. Finally, well characterized gold (I) complexes have systematically been evaluated for in vitro cytotoxic activity against various human cancer cell lines e.g. A549 (human lung carcinoma), MCF7 (human breast cancer), and HeLa (human cervical cancer) cell lines.